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The combination of synthetic disease-modifying anti-rheumatic drugs (sDMARDs) such as methotrexate (MTX) and biologic DMARDs (bDMARDs) targeting inflammatory cytokines such as tumour necrosis factor (TNF) has enabled markedly efficient control of disease activity in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR).1–7 Although TNF inhibitors have offered pivotal strategies for rheumatologists in daily practice and 20–50% of RA patients treated with TNF inhibitors achieve clinical remission within 6 months, the remaining patients still have active disease and progressive disability. IL-6 is also a pleiotropic cytokine with diverse activities and plays a central role in the pathogenesis of RA by contributing to T cell activation, B cell activation, synoviocyte stimulation, endothelial activation, osteoclast maturation and production of acute-phase proteins. Serum levels of IL-6 and soluble IL-6 receptor (IL-6R) are elevated and correlate with disease activity in RA patients and so blocking IL-6/IL-6R has been considered beneficial for the treatment of RA. In accordance with this, accumulated evidence has shown the clinical efficacy as well as the adequate safety of tocilizumab, a humanised anti-IL-6R monoclonal antibody (mAb), as monotherapy or in combination with sDMARDs such as MTX in patients who are sDMARD naive and have an inadequate response to TNF inhibitors (TNF-IR).8–13 Tocilizumab was, therefore, approved as a first-line bDMARD in patients responding insufficiently to MTX or other sDMARDs in Japan and Europe. Also, in the 2013 EULAR recommendations for the management of RA, tocilizumab was listed as a first-line TNF inhibitor in patients with sDMARD-IR.14 The successful treatment of RA by tocilizumab has encouraged the development of novel bDMARDs targeting IL-6 or IL-6R. In addition to tocilizumab, the phase II clinical trials of olokizumab, sarilumab and sirukumab, three new bDMARDs targeting IL-6, are reported.
Olokizumab is a humanised anti-IL-6 mAb. Genovese et al15 report the …
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